The Future of Catheter Ablation

The Future of Catheter Ablation KH Kuck, MD Asklepios Klink St. Georg, Hamburg

Disclosure Statement Research Grants Consultant / Advisory Board Ownership Interests Speaker s Bureau Honoraria Biosense Webster, Stereotaxis, Medtronic, St. Jude, Cardiofocus, Abbott St. Jude, Edwards, Stereotaxis, Mitralign, Cardiofocus, BMDSys, ACT, Maya, Apama, Topera, Recor, Endosense, SynapticMed, Shareholder Endosense Biosense Webster, Medtronic, St. Jude, Abbott, Cardiofocus, Biotronik Fellowship Support None Other Off-label drugs/devices None None

EP - Catheter ablation Trigger ablation in AF Substrate identification- rotors and sources Lesion formation/assessment Contact force, intramural temperature measurement Direct visualisation of the anatomy/substrate

Catheter ablation of atrial fibrillation LPVs * LAA RPVs MA * Haissaguerre M et al (N Eng J Med 1998; 339: 659 66)

Irrigated tip, max 30 W in posterior wall and roof, max 40 W at other sites Ouyang et al, Circulation 2004

Atrial Fibrillation-Catheter ablation The mean follow-up period was 14 months, with a range from 2 to 30 months Calkins et al, Circ Arrhythmia Electrophysiol. 2009;2:349-361

R. Cappato et al, JACC 2009 Major Complications AF Survey II Type of Complication No of Pts Rate,% Death 25 0.15 Tamponade 213 1.31 Pneumothorax 15 0.09 Haemothorax 4 0.02 Sepsis, abscesses or endocarditis 2 0.01 Permanent diaphragmatic paralysis 28 0.17 Total femoral pseudoaneurysm 152 0.93 Total artero-venous fistulae 88 0.54 Valve damage/requiring surgery 11/7 0.07 Atrium-esophageal fistulae 3 0.02 Stroke 37 0.23 Transient ischaemic attack 115 0.71 Pulmonary veins stenoses requiring intervention 48 0.29 Total 741 4.54

1.5 ± 0.6 procedures/pt 80.8% 58.6% F Ouyang et al. Circulation 2010

Freedom from ATa Single Procedure Success-longstanding pers AF Follow up: 56.3 (Q1,Q3; 49.1; 66.8) month Sinus Rhythm in 20.3% Tilz et al., JACC 2012

Freedom from ATa Multiple Procedure Success-longstanding pers AF Follow up: 49.5 (Q1, Q3; 35.7; 61.2) month Sinus Rhythm in 45.0% Tilz et al., JACC 2012

Future AF ablation Improved understanding of mechanisms of persistent forms of AF Improved ablation Information on lesion formation (size, depth, transmural) Other energy sources, direct visualisation ( cryo, Laser, etc)

Which AF Mechanisms are targeted by Ablation? Left Atrium Mechanistically, are AF ablation targets: 1. Anatomic drivers (e.g. PVs, ganglia 3 ) 2. Rapid sites 4 (high dominant frequency) 3. Organized sites (narrow DF) 4? 4. Disorganized sites (CFAE, fractionated 5 )? 5. Other (1) Calkins, Heart Rhythm 2007; 4:816-861. (2) Haissaguerre, NEJM 1998; 659-666; (3) Scherlag J Int Card EP 2005;37-42; (4) Sanders, Circulation 2005;789-797; (5) Nademanee, JACC 2004;2044-2053;

Hypothesis: Stable Sources Perpetuate AF Electrical Rotor ( Driver ) X Optically Mapped Sheep atria 1,2 Sometimes stable, often migratory 1,2 In human AF: Little or no direct evidence for rotors 1-5 If Stable, Attractive Sites For Localized Ablation (1) Vaquero/Jalife Heart Rhythm 2008;872-879; (2) Skanes Circulation 1998; 1236-48; (3) de Groot NM, Allessie MA. Circulation. 2010; 1674-1682; (4) Allessie, Cardiovasc Res 2002; 230-246; (5) Cuculich, Rudy. Circulation 2010; 1364-1372

CONventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation The CONFIRM trial tests the hypotheses that: (1) AF in patients is caused by localized electrical rotors or focal beats, visualizable for the first time using a novel physiological mapping system; (2) Localized ablation (Focal Impulse and Rotor Modulation, FIRM) will acutely terminate or slow AF and, when added to conventional anatomic (pulmonary vein) ablation, improve long-term AF elimination compared to conventional ablation alone.

Methods: Patient-Tailored Physiological Mapping of AF Development of a Novel Diagnostic System Reentrant Path, l = ERP x CV Rensma, Circ Res 1988: 395-410.; Narayan, Circ 2002; 1968-1973; Narayan JACC 2008; 1222-1230; Narayan, Heart Rhythm 2011; 244-253; Narayan, Circulation 2011, in press; Lalani, 2011 in review

Rotor During Human AF 66 YO man, Paroxysmal AF; Left Atrial diameter 42 mm; LVEF 56 %

RA Rotor with LA activation

LA Rotor with passive activation of RA

Patient Demographics (n=103) Characteristic Conventional FIRM-Guided P Number 71 32 Persistent AF, n (%) 45 (63%) 24 (75%) 0.25 Age /years (range) 61±8 (40-82) 63±10 (43-82) 0.43 History of AF /years 5.0±6.8 (0.5-31.8) 7.0±6.3 (1.6-31.2) 0.23 LA diameter /mm (range) 43±6 (30-58) 47±7 (38-62) <0.01 LVEF /% (range) 56±11 (21-75) 56±15 (20-79) 0.99 Hypertension / n (%) 49 (69) 26 (81) 0.20 Coronary Disease / n (%) 30 (42) 15 (47) 0.66 Medications / n (%) Previously ineffective AAD 1.7±1.1 1.9±1.0 0.78 ACEI/ARB 41 (58) 14 (44) 0.19 Statins 41 (58) 17 (53) 0.66 Followup with CIED /n (%) 16 (23) 27 (84) <0.001 First patient enrolled October 5 th, 2005

FIRM at Inferior Left Atrial Rotor Terminates AF to Sinus in < 1 minute 81 YO man, AF for 31 Years, Multiple Cardioversions

Summary Results: Acute Endpoint Characteristic Conventional FIRM-Guided P No. Pts with Sustained AF 63 32 No. with Rotors/Foci, n/% 61 (97%) 32 (100%) 0.31 No. Sources / patient 1.9±0.8 2.1±0.8 0.28 Acute AF termination/slowing 9 (14%) 28 (88%) <0.001 (in <30 minutes of ablation), n (%) AF Termination, n (%) 9 (14%) 20 (63%) <0.001 Sinus/Atrial Tachycardia 4/5 17/3 0.030 Time to Termination/mins 23.5±7.7 6.6±4.9 <0.001 AF Slowing >10%, n (%) Early Version of Diagnostic 0 8 (25%) <0.001 AF CL prolongation, System ms (map (%) only 1 source) 29±5 (17±3%) Other Not targeted* 2 pts * (1) Phrenic nerve capture; (2) at pacing lead

CONFIRM Trial: Long-Term Single Procedure Efficacy FIRM-Guided, 84.3% (84% had Implanted Monitors) Conventional, 50.5% (23% had Implanted Monitors) P=0.04

EP - Catheter ablation Trigger ablation in AF Substrate identification- rotors and sources Lesion formation/assessment Contact force, intramural temperature measurement Direct visualisation of the anatomy/substrate

What Parameters Drive Lesion Quality? Contact force (g) Goal: Lesion depth Duration (s) Power (W) Complication Risk Temperature ( C)

Key Challenge: Force Control A Balancing Act between Efficacy and Safety Insufficient Contact Lengthy procedure 20-50% Redo procedures Wide center effectiveness variability Excessive Contact Risk of tamponade Risk of esophageal injury Risk of steam pops

Optical Tri-axial Force Sensing (Endosense) Force sensor at catheter tip with real time contact force and angle measurement Sensitivity: one gram Fully integrated system Comparable to currently used irrigated ablation catheter with the addition of the force sensor

Lesion size significantly increases with increased contact force Risk of pop formation increases with increasing force and power Higher contact force allows for lower RF power at same lesion quality Thiagalingam A et al, Importance of catheter contact force during irrigated radiofrequency ablation: evaluation in a porcine ex vivo model using a force-sensing catheter J Cardiovasc Electrophysiol. 2010 Jul;21(7):806-11

Significant Force Variability by Operator TOCCATA STUDY KEY ACUTE OUTCOME 68 Recommended work area Kh Kuck et.al.; A novel radiofrequency ablation catheter using contact force sensing: Toccata study, Heart Rhythm, oi:10.1016/j.hrthm.2011.08.021

EFFICAS Clinical Study overview 3 center study (Hamburg, Prague Homolka, Prague IKEM) EFFICAS I: Operator blinded to contact force information EFFICAS II: Operator NOT blinded & actively uses contact force to optimize ablation EFFICAS I EFFICAS II Study Design Single arm prospective Ablation parameters Blinded to CF, standard RF Guidelines for use of CF Endpoint Gap vs no gap Less # of gaps Atrio-PV delay Study endpoint measure Interventional EP outcome after 3 months CF: contact force

Efficas I main findings Minimum Contact Force and minimum FTI are determinants for gap occurrence at 3 months. Each ablation is important! Any ablation with FTI < 300 g.s reduces probability for successful outcome by 23% 100% 95% 90% 85% 80% 75% Success ratio per segment Minimum FTI 44 153 3 24 5 91 <300 g.s. [300;400]g.s. >400 g.s. The number of ablations correlate inversely with success. Any bad ablation is difficult to correct. Edema formation might be an important factor preventing transmural lesions N = 52 N = 266

Contact Force guidance 1. Target 20g of Contact Force with range [10g, 30g] 2. Min FTI is determinant Absolute minimum 400 g.s. Target 600-800 g.s

% of ablations Better control of Contact Force 25% 20% 15% 10% 5% 0% Relative Ablations distribution by Force EFF 1: 44 patients, 3017 ablations 25% 20% 15% 10% 5% 0% Ablations distribution by Force EFF 2: 43 patients, 2279 ablations 60 50 40 30 20 10 0 Force [g] Contact Forces distribution (g) 52,0 43,6 25,2 26,4 14,9 18,1 12,9 7,8 6,9 2,7 EFFICAS I EFFICAS II 25% 5% 50% 95% 75% Force [g] 23% more ablations within Contact Force recommendation [10 g, 30 g]

% of ablations Better control of FTI 30% Relative ablations distribution by FTI EFF 1: 44 patients, 3017 ablations 30% Relative ablations distribution by FTI EFF 2: 43 patients, 2279 ablations 20% 20% 10% 10% 0% 0% FTI [g.s.] FTI distribution (gs) 2400 2000 2206 1600 1697 1200 800 952 959 641 400 474 447 0 229 49 100 EFFICAS I EFFICAS II 25% 5% 50% 95% 75% FTI [g.s.] + 24% ablations following FTI recommendation > 400 gs

Minimum Force Parameters EFFICAS & Model Force (g) 15 10 5 0 Min Force (g) 13 7 p=0.001 Every added dimension increases gap predictability Time FTI (gs) 500 0 Min FTI (gs) 436 213 p < 0.001 6 Min LSI p < 10-5 Confidential Power (W) 4 2 0 4,2 Efficas I data - FTI TM : Force Time Integral - LSI TM : Lesion Index 2,9

What Parameters Drive Lesion Quality? Contact force (g) Goal: Lesion depth Duration (s) Power (W) Complication Risk In-Tissue Temperature ( C)

In-Tissue Temperature Nath S, et al.cellular electrophysiological effects of hyperthermia in isolated guinea pig papillary muscle: Implications for catheter ablation. Circulation 1993;88(4 Pt1):1826-1831.

Microwave Radiometry Measures microwaves coming off a heat source Measures heat generated microwaves at a distance which are directly correlated to the temperature inside the tissue Microwaves are not disturbed by irrigation Independent of catheter position

7F 3.5 mm Tip Irrigated RF Ablation Catheter with Built-in Radiometery Chip

Improving Lesion Formation Temperature heating at 3mm depth within tissue Approximate lesion volume Quality of continuous contact during ablation

Example of Thigh Run 20 W Testing U of OK Courtesy Dr. Jackman/Nakagawa

Participating Centers AZ St. Jan Hospital AZ Brussels Brussels Askeplios Clinic Charles University Czech Republic ChristChurch University Antonius Hospital Netherlands Brugge Hamburg New Zealand

1 st Flutter Patient Ablation 18,19,20 Courtesy Dr. Vandekerckhove - Brugge

Catheter ablation Fluoroscopy/simple substrates 3-D-Mapping/complex substrates Lesion formation/assessment Direct visualisation of the anatomy/substrate

Visually-Guided Ablation Static Blood in Occluded Vein Aiming Beam Free-Flowing Blood Proximal to Balloon

Compliant Balloon: Dynamic Sizing

Visually-Guided Ablation: Clinical Experience

Is Visually-Guided ablation permanent? Study : Ablation in 10 pts EP study at 10 weeks in all patients (regardless of sxs) 8 pts agreed to 2 nd procedure Results: 8 patients 28 PVs Persistent Isolation 28/30 PVs (93%) Courtesy of V Reddy

Catheter ablation Conclusions Catheter ablation is a perfect example for a successful cooperation between industry and physicians